Sunday, September 22, 2013

Air Pollution and the Gut: Are Fine Particles Linked to Bowel Disease?

Sun, Sep 22, 2013 at 7:43 AM

At 22, Mark Rievaj had one major love: speed skating. Day and night he spent at the Calgary track, vying for a coveted position on Canada’s national team. He was having the best season of his amateur career when he noticed a small fissure on his anus. “I was losing blood, not much, but a little bit every day,” Rievaj recalls.

For months, his doctors struggled to make a diagnosis as Rievaj’s iron levels — and energy — plummeted and his skating performance faltered. Finally, he learned that he had Crohn’s disease.

Worldwide, an estimated 5 million people suffer from Crohn’s or ulcerative colitis, diseases of the gastrointestinal tract collectively referred to as Inflammatory Bowel Diseases. In recent years, scientists have identified genes that may account for as much as 25 percent of these diseases. But now they are beginning to look beyond the human genome to the environment for answers. A small but growing number of studies now suggest that air pollutants may play a role in diseases of the gut.

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The impacts of air pollution on the lungs and the heart have been widely documented for decades. But until now, few researchers have paid attention to the gastrointestinal tract.

“We tend to think about air pollution in terms of lung health, but the GI tract is also being bathed in it continuously. Fine pollution particles are cleared from the respiratory tract by mucous that makes its way to the gut,” said Karen Madsen, a gastroenterological scientist from the University of Alberta in Edmonton.

Some evidence suggests inhaling fine particles, or soot, may disrupt the immune system and trigger inflammation in the gut by making it more permeable and altering its normal bacteria.

Tiny airborne particulates, which come mostly from fuel combustion, are a worldwide problem. In the United States, more than 44 million people live in areas that exceed federal health standards for fine particles, according to the American Lung Association.

Edmonton, the capital of Alberta, ranked as the Canadian city with the highest average annual levels of fine particulate matter in 2010, with levels similar to those of Chicago, almost three times its size. Forest fires, car exhaust and fuel for heating homes and businesses are major sources in Alberta.

Doctors say Mark Rievaj's children are at risk of inheriting his Crohn's disease because 25 percent of cases are tied to genes.

In Rievaj’s native Canada, one-half of 1 percent of the population is thought to suffer from bowel diseases — the highest incidence of any country. There are likely many reasons for the high rate. Scientists in Canada, including Madsen and Rievaj’s own doctor, Dr. Gilaad Kaplan, a gastroenterologist at the University of Calgary in Alberta, are combing the environment for clues.

“Understanding the risk factors can help us to mitigate the risk and prevent people from getting the disease in the first place,” Kaplan said.

Yet “we’re still very early in our understanding of the role air pollution may play in gastrointestinal disease,” said Dr. Eric Benchimol, a pediatric gastroenterologist at Children’s Hospital of Eastern Ontario in Ottawa.

One study by Kaplan and colleagues found that people in the United Kingdom between the ages of 5 and 23 with higher exposure to nitrogen dioxide, a component of traffic exhaust, were more than twice as likely to develop Crohn’s disease as young people with less exposure. However, no association was found between newly diagnosed cases of bowel diseases as a whole and total levels of air pollution.

Also, a study of hospital admissions in Wisconsin found that high air pollution emissions were associated with a 40 percent increase in the rate of bowel disease hospitalizations in 2002. The authors accounted for carbon monoxide, sulfur dioxide, nitrous oxide, volatile organic chemicals and fine particulate matter.

“Do I think air pollution is the cause of Crohn’s disease or ulcerative colitis? Definitely not,” Kaplan said, “but it may contribute to the complex nature of how these diseases develop.”

Kaplan’s team also found that in Montreal and Edmonton, emergency room visits for abdominal pain without a known cause were slightly higher among 15- to 24-year olds on days when levels of certain air pollutants were elevated.

Another study found a link between smog and appendicitis. High levels of ozone, the main ingredient of smog, were linked to an increased risk of a burst appendix in a study of more than 35,000 people across 12 Canadian cities between 2004 and 2008. Kaplan and colleagues estimated an 11 to 22 percent increased risk of burst appendix with every increase of 16 parts per billion of ozone averaged over the previous seven days.

It’s unclear how, exactly, air pollution could contribute to gastrointestinal disease, but some experts believe bacteria may have something to do with it. Many of the 160 gene regions implicated in the development of bowel diseases also regulate how the immune system recognizes and interacts with the trillions of bacteria that exist in the human gut.

“In the gut, you have a barrier between the immune system and the bacteria that live there. It’s important that barrier gets maintained,” Madsen said.

Air pollution particles may disrupt the barrier by making the gut more permeable to bacteria and possibly altering the composition of the bacteria. Studies with mice show that pollution particles make the gut more permeable.

“For me personally, I don’t know that the research will have much of an impact. But my four kids, who are at a higher risk of developing the disease, I hope it helps them.” —Mark Rievaj “Those changes can lead to inflammation and may set up someone who is genetically predisposed to inflammatory bowel diseases,” Kaplan said. Madsen added that gut permeability plus genetic defects “are a real double whammy.”

Other studies have shown that air pollution may lead to an increase in inflammatory particles called cytokines circulating throughout the body, including the gut. Some of these particles may play a role in the development of bowel diseases.

“The interplay between the gut microbiome and the immune system is really on the forefront of IBD research. The air pollution research looks promising, but right now it’s still too soon to know for sure whether the link is real,” said Dr. Melissa Rosen, a gastroenterologist at New York University’s Langone Medical Center.

Nevertheless, patients such as Rievaj will likely never be able to pinpoint the exact cause of their disease.

Along with air pollution, smoking, low vitamin D levels, growing up in an urban environment and eating a lot of meats and sugars have all been implicated as risk factors for bowel diseases.

“No one factor explains the whole story. Each is just one part of an incomplete puzzle. We are just now collecting the pieces and starting to put them on the table,” Kaplan said.

Rievaj didn’t give much thought to what factors may have caused his disease. “When I first got the diagnosis, I didn’t want to listen to the doctors who told me I might not be able to compete at that level anymore. Like any athlete, I wanted to be the anomaly.”

But the physical limitations proved too much. After two years, Rievaj hung up his skates for good. “One of the most frustrating things was not being able to retire on my own terms,” he said.

The years of intestinal inflammation also have taken a toll on other systems of his body. Rievaj suffers from the highest stage of liver cirrhosis; he will need a new liver in the next few years and may face the removal of his entire large intestine.

“For me personally, I don’t know that the research will have much of an impact,” he said. “But my four kids, who are at a higher risk of developing the disease, I hope it helps them.”